Polycomb proteins link Proliferation with DNA Replication
ABSTRACT: Polycomb proteins control proliferation and cellular transformation regulating DNA replication independently of cell cycle checkpoints Total RNA was extracted from MEF cells (derived from Ola129 mice) transiently transfected with Ezh2 specific and control esiRNA oligos 48 hrs. post-transfection.
Project description:O-linked N-acetylglucosamine (O-GlcNAc ) transferase (OGT) activity is essential for embryonic stem (ES) cell viability and mouse development. OGT is present in both cytoplasm and nucleus of different cell types and mediates serine or threonine glycosylation. The Ogt gene locus resides on the X-chromosome and its activity is required for the viability of male ES cells. Using Ogt conditional knock out (KO) ES cells it was shown the failure of establishing stable KO ES clones further suggesting that Ogt activity is required for ES cell self-renewal and pluripotency. For understanding these changes, we performed global gene expression upon silencing of Ogt mediated by esiRNA in mouse Embryonic Stem Cells. Total RNA was extracted from E14 ES cells (derived from Ola129 mice) transiently transfected with Ogt specific and control esiRNA oligos 48 hrs. post-transfection.
Project description:We have determined the global gene expression upon loss of function of the Yy1 transcription factor in mouse embryonic stem cells Total RNA was extracted from ES cells transiently transfected with yy1-specific or scrampled-control siRNA oligos 48 hr post-transfection.
Project description:This SuperSeries is composed of the following subset Series: GSE31784: Expression changes in Yy1 knock down mouse embryonic stem cells GSE31785: Yy1 occupancy of mouse ES cell genome Refer to individual Series
Project description:Pan-Hdac inhibitors (HDACi) are endowed with a potent anti-inflammatory activity, but the relative role of each of the eleven Hdac proteins sensitive to HDACi to the inflammatory gene expression program is unknown. Using an integrated genomic approach we found that Hdac3-deficient macrophages are unable to activate almost half of the inflammatory gene expression program when stimulated with lipopolysaccharide (LPS). A large part of the activation defect is due to loss of basal and LPS-inducible expression of IFNb, which in basal cells maintains Stat1 protein levels, and after stimulation acts in an autocrine/paracrine manner to promote a secondary wave of Stat1-dependent gene expression. We show that loss of Hdac3-mediated repression of nuclear receptors leads to hyperacetylation of thousands of genomic sites and associated gene derepression. The upregulation of the constitutively expressed prostaglandin endoperoxide synthase, Ptgs1 (Cox-1), has a causative role in the phenotype, since its chemical inhibition reverts the Ifnb activation defect. These data may have relevance for the use of selective Hdac inhibitors as anti-inflammatory agents. Gene expression profiles for bone marrow-derived macrophages from either HDAC3 +/- (wt) or HDAC3 -/- (KO). Cells were left untreated or challenged with lipopolysaccharide (LPS) for 4hrs. Each genotype-treatment combination was performed in triplicate.
Project description:This SuperSeries is composed of the following subset Series: GSE33162: HDAC3 requirement for the inflammatory gene expression program in macrophages [gene expression] GSE33163: HDAC3 requirement for the inflammatory gene expression program in macrophages [ChIP_Seq] Refer to individual Series
Project description:Histone methyltransferases catalyze site-specific deposition of methyl groups, enabling recruitment of transcriptional regulators. In mammals, trimethylation of lysine 4 in histone H3, a modification localized at the transcription start sites of active genes, is catalyzed by six enzymes (SET1a and SET1b, MLL1–MLL4) whose specific functions are largely unknown. By using a genomic approach, we found that in macrophages, MLL4 (also known as Wbp7) was required for the expression of Pigp, an essential component of the GPI-GlcNAc transferase, the enzyme catalyzing the first step of glycosylphosphatidylinositol (GPI) anchor synthesis. Impaired Pigp expression in Wbp7-/- macrophages abolished GPI anchor-dependent loading of proteins on the cell membrane. Consistently, loss of GPI-anchored CD14, the coreceptor for lipopolysaccharide (LPS) and other bacterial molecules, markedly attenuated LPS-triggered intracellular signals and gene expression changes. These data link a histone-modifying enzyme to a biosynthetic pathway and indicate a specialized biological role for Wbp7 in macrophage function and antimicrobial response. Gene expression profiles for bone marrow-derived macrophages (BMDM) from either Wbp7+/- (HET) or Wbp7-/- (KO). Cells were left untreated or challenged with lipopolysaccharide (LPS) for 2hrs or 4hrs. Each genotype-treatment combination were performed in triplicate.
Project description:Human adipose tissue contains two populations of progenitors (EPCs and ASCs) with cooperative roles in breast cancer. EPCs (CD45-CD34+CD31+CD13-CCRL2+) can generate endothelial cells. ASCs (CD45-CD34+CD31-CD13+CD140b+) are mesenchymal progenitors which generated pericytes. CD13+ cells and CD13- cells from 7 Lipotransfer aspirate
Project description:A catalytic role has been proposed in neoplastic angiogenesis and cancer progression for bone marrow-derived endothelial progenitor cells (EPCs). However, in preclinical and clinical studies the quantitative role of marrow-derived EPCs in cancer vascularization was found to be extremely variable. Adipose tissue represents an attractive source of autologous adult stem cells due to its abundance and surgical accessibility. CD34+cells from Lipotransfer aspirates (LAs) of patients undergoing breast reconstruction after breast cancer surgery were compared with CD34+ cells from Leucapheresis of normal subjects. Two samples of purified CD34+ cells from Lipotransfer Aspirates (LAs) were compared with two samples of CD34+ cells from Leucapheresis samples. The reference were considered the CD34+ RNA from leucapheresis
Project description:This SuperSeries is composed of the following subset Series: GSE30971: The Histone Methyltransferase Wbp7 Controls Macrophage Function through GPI Glycolipid Anchor Synthesis. [Expression Profile] GSE30972: The Histone Methyltransferase Wbp7 Controls Macrophage Function through GPI Glycolipid Anchor Synthesis. [ChIP_seq] Refer to individual Series